The Scoop on Sirtuins

Everyone in the skin care world is talking about sirtuins. Studies have shown that resveratrol activates sirtuins, and sales of resveratrol have risen. Many products claim to contain ingredients that activate sirtuins.

To be up to date on current skin care, you need to know what sirtuins are and why they are a frequent topic at the Society of Cosmetic Chemists meetings. The short explanation is that calorie-restricted mice have been shown to live longer and to have increased expression of sirtuins. It is believed that the upregulation of sirtuin expression is associated with increased longevity. When mice were not calorie restricted but were treated with resveratrol to activate sirtuins, they also lived longer.

The current belief that activating sirtuin is desirable has led to a plethora of products with sirtuin-activating ingredients, including several sold by Avon Products Inc.

Where Are Sirtuins Found?

Role of Sirtuins
Silent mating type information regulator 2 (Sir2) proteins, or sirtuins, are a family of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes known to deacetylate lysine residues on several proteins and, in some cases, to exhibit adenosine diphosphate (ADP)-ribosyltransferase activity (Genome Biol. 2004;5:224; Mol. Endocrinol. 2007;21:1745-55). Sirtuins are activated when cellular energy is low and the NAD+ to NADH ratio is high (Genes Nutr. 2006;1:85-93).

This family of enzymes is known to be involved in apoptosis, fatty acid metabolism, gene silencing, and regulation of cellular lifespans. They are also linked to genes that organize and optimize cell functions to resist or survive in stressful environments (J. Drugs Dermatol. 2007;6:s14-9). Sirtuins regulate important biological pathways, such as transcriptional repression, recombination, the cell-division cycle, microtubule organization, and cellular responses to DNA-damaging compounds (Genome Biol. 2004;5:224).

It is believed that the mammalian sirtuins, SIRT1-SIRT7, play an influential role in gene silencing, energy homeostasis, the cell cycle, apoptosis, stress resistance or stress responses, axonal degeneration, and aging (Genome Biol. 2004;5:224; Mol. Endocrinol. 2007;21:1745-55; J. Cell Mol. Med. 2008 Aug 4 [doi:10.1111/j.1582-4934.2008.00453.x ]). As such, Yamamoto et al. have contended that sirtuins may be appropriate therapeutic targets for a range of disorders, including proliferative, neurodegenerative, and metabolic diseases (Mol. Endocrinol. 2007;21:1745-55).

The Nomenclature

Sirtuin Research in Skin

For the active skin care product portion of the study, the researchers enrolled 33 women between 37 and 64 years old (mean age 51.6 years), who were instructed to apply a formulation enriched in 1% of the yeast biopeptides once daily for 4 weeks to the neck and face. Before and after the first application and after 4 weeks of use, investigating dermatologists assessed fine lines and wrinkles, pigment color intensity, complexion homogeneity, and radiance, as well as skin density, hydration, firmness, and texture on a 1-9 scale. To objectively evaluate skin care efficacy, they used a pixel skin method based on analyzing age-related parameters from numerical pictures of faces.

The investigators identified multiple findings from their study. In particular, the Kluyveromyces biopeptides markedly increased SIRT1 expression in normal human dermal fibroblasts in vitro as well as in healthy human epidermal cells ex vivo while diminishing cellular aging and UVB-induced DNA fragmentation. Among the study participants, improvements were found in all of the assessment parameters, with hydration noted as significantly improving right after the first application.

The authors concluded that the yeast Kluyveromyces biopeptides were efficacious in activating SIRT1 in human skin cells, resulting in the enhancement of DNA resistance and aging. In addition, a formulation featuring Kluyveromyces biopeptides exhibited efficacy in ameliorating various signs of cutaneous aging (J. Drugs Dermatol. 2007;6:s14-9).

In 2008, Cao et al. reported on the role of SIRT1 in UV signaling pathways. With cell culture and Western blot analysis, they found that SIRT1 is expressed in cultured human skin keratinocytes. The investigators observed that SIRT1 is time- and dose-dependently down-regulated by exposure to UV radiation and H2O2, with reactive oxygen species (ROS)-mediated JNK (c-Jun N-terminal kinase) activation involved in the down-regulation. Significantly, resveratrol, an activator of SIRT1, protected against UV- and H2O2-induced apoptosis; SIRT inhibitors such as sirtinol and nicotinamide promoted apoptosis.

The investigators also noted that resveratrol suppresses UV- and H2O2-induced p53 acetylation, while the SIRT inhibitors sirtinol and nicotinamide, as well as SIRT1 small interfering RNA (siRNA), foster it. Overall, the researchers suggested that their work adds to the understanding of the molecular mechanisms of photoaging, and that the SIRT1-activating property of resveratrol might be targeted in agents intended for therapeutic approaches to cutaneous aging (J. Cell Mol. Med. 2008 Aug 4 [doi:10.1111/j.1582-4934.2008.00453.x]).

Also in 2008, Pallàs et al. found that increasing SIRT1 protects against amyloid beta-induced ROS synthesis and DNA damage, thus diminishing in vitro apoptosis. In addition, the overexpression of SIRT1, induced by caloric restriction or the use of the antioxidant resveratrol, has been shown to rescue Alzheimer's and Huntington's disease neurons (Recent Pat. CNS Drug Discov. 2008;3:61-9). SIRT1 and SIR2 had already been implicated as the proteins involved in lifespan extension from caloric restriction in various species.

Polyphenols such as quercetin and resveratrol are dietary antioxidants known to confer numerous health benefits and to activate sirtuins, thus playing a role in the caloric restriction longevity extension mechanism; their capacity to influence or extend lifespan has been shown in simple organisms but not consistently, as yet, in humans or other mammals (J. Cosmet. Dermatol. 2008;7:2-7; Genes Nutr. 2006;1:85-93).

However, work in mice (discussed in an episode of the television show "60 Minutes" in early 2009) performed by Sirtris Pharmaceuticals, a research company founded on recent discoveries related to sirtuins, demonstrated that resveratrol fed to mice on a high-fat diet improved insulin resistance, increased mitochondrial content, and prolonged life. In two groups of mice fed a high-fat diet, both groups wound up obese, but the mice administered resveratrol as part of their diet were able to run twice as far and fast, and survived 20% longer. In other studies by Sirtris, mice fed resveratrol as part of a high-fat diet gained less weight than mice administered a high-fat diet without resveratrol. Investigators at Sirtris also have identified small-molecule activators of SIRT1 that are 1,000 times as strong as resveratrol (Nature 2007;450:712-6).

Many other companies, such as Avon, have studied ingredients that upregulate sirtuin expression. By using human skin biopsies and immunohistochemical analysis, Avon has shown that its own proprietary botanical extracts promote the expression of dermal matrix proteins. The company claims that a 12-week clinical study using a product formulated to stimulate sirtuin expression displayed efficacy that warrants use in an antiaging product.

It remains to be seen what such claims - and products - will mean for the skin. For now, I would continue to recommend oral resveratrol and red wine supplements. In particular, I suggest OPC Synergy by Standard Process Inc., which contains grape seed and red wine extracts.

Conclusions
The family of proteins known as sirtuins appears to play an important role in the increased lifespan of various species, particularly, as recent research suggests, in calorie-restricted animals. The polyphenolic antioxidant resveratrol, which is abundant in red wine and is now included in some cosmeceutical agents, upregulates sirtuin expression and may protect cells from DNA damage.

The discovery of the role of sirtuin expression in slowing the pace of aging, in the experimental setting, strikes me as a very significant advance, and may lead to further elucidation of the aging process overall as well as cutaneous aging.

However, it is unknown at this time what role sirtuin and sirtuin activators play in skin care. Early data suggest that the activation of sirtuins may improve the appearance of skin, but the mechanism, if known, is unclear to me. The potential of Avon's botanically derived agent in upregulating sirtuin expression in skin cell cultures appears promising, because the company's study did reveal that patients experienced improvement in wrinkles. I was not the investigator in this study, so it is difficult to comment on the validity of the observations, as I am unsure of the exact study design.

I will be interested to see further work in this area, and it's always good to have a medically sound reason to drink wine.

Recently, investigators attempted to stimulate the expression of sirtuin, specifically SIRT1, in human skin cells in a culture of yeast Kluyveromyces biopetides, and to identify cutaneous benefits from an active skin care product containing such biopeptides. They also tested healthy skin samples ex vivo. Immunostaining, Western blotting, and cytometry were used to assess SIRT1 in culture and in ex vivo samples. Comet assays were used to evaluate cellular aging and integrity. Sir2 protein (Sir2p), present in yeast, is the founding member of the sirtuin family. SIRT1 was the first homolog found in humans and other mammals (Mol. Endocrinol. 2007;21:1745-55; Mol. Cell Biol. 2003;23:3173-85; Biochem. Biophys. Res. Commun. 2000;273:793-8). Now there are seven known mammalian sirtuins: SIRT1-SIRT7. Sirtuins are found in organisms ranging from bacteria to humans. Much sirtuin research has been done in the yeast Saccharomyces cerevisiae, the fruit fly Drosophila melanogaster, and the nematode Caenorhabditis elegans. In these organisms, sirtuins have been identified as molecules that mediate the effects of caloric restriction on aging processes (Genes Nutr. 2006;1:85-93).

Everyone in the skin care world is talking about sirtuins. Studies have shown that resveratrol activates sirtuins, and sales of resveratrol have risen. Many products claim to contain ingredients that activate sirtuins.

To be up to date on current skin care, you need to know what sirtuins are and why they are a frequent topic at the Society of Cosmetic Chemists meetings. The short explanation is that calorie-restricted mice have been shown to live longer and to have increased expression of sirtuins. It is believed that the upregulation of sirtuin expression is associated with increased longevity. When mice were not calorie restricted but were treated with resveratrol to activate sirtuins, they also lived longer.

The current belief that activating sirtuin is desirable has led to a plethora of products with sirtuin-activating ingredients, including several sold by Avon Products Inc.

Where Are Sirtuins Found?

Role of Sirtuins
Silent mating type information regulator 2 (Sir2) proteins, or sirtuins, are a family of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes known to deacetylate lysine residues on several proteins and, in some cases, to exhibit adenosine diphosphate (ADP)-ribosyltransferase activity (Genome Biol. 2004;5:224; Mol. Endocrinol. 2007;21:1745-55). Sirtuins are activated when cellular energy is low and the NAD+ to NADH ratio is high (Genes Nutr. 2006;1:85-93).

This family of enzymes is known to be involved in apoptosis, fatty acid metabolism, gene silencing, and regulation of cellular lifespans. They are also linked to genes that organize and optimize cell functions to resist or survive in stressful environments (J. Drugs Dermatol. 2007;6:s14-9). Sirtuins regulate important biological pathways, such as transcriptional repression, recombination, the cell-division cycle, microtubule organization, and cellular responses to DNA-damaging compounds (Genome Biol. 2004;5:224).

It is believed that the mammalian sirtuins, SIRT1-SIRT7, play an influential role in gene silencing, energy homeostasis, the cell cycle, apoptosis, stress resistance or stress responses, axonal degeneration, and aging (Genome Biol. 2004;5:224; Mol. Endocrinol. 2007;21:1745-55; J. Cell Mol. Med. 2008 Aug 4 [doi:10.1111/j.1582-4934.2008.00453.x ]). As such, Yamamoto et al. have contended that sirtuins may be appropriate therapeutic targets for a range of disorders, including proliferative, neurodegenerative, and metabolic diseases (Mol. Endocrinol. 2007;21:1745-55).

The Nomenclature

Sirtuin Research in Skin

For the active skin care product portion of the study, the researchers enrolled 33 women between 37 and 64 years old (mean age 51.6 years), who were instructed to apply a formulation enriched in 1% of the yeast biopeptides once daily for 4 weeks to the neck and face. Before and after the first application and after 4 weeks of use, investigating dermatologists assessed fine lines and wrinkles, pigment color intensity, complexion homogeneity, and radiance, as well as skin density, hydration, firmness, and texture on a 1-9 scale. To objectively evaluate skin care efficacy, they used a pixel skin method based on analyzing age-related parameters from numerical pictures of faces.

The investigators identified multiple findings from their study. In particular, the Kluyveromyces biopeptides markedly increased SIRT1 expression in normal human dermal fibroblasts in vitro as well as in healthy human epidermal cells ex vivo while diminishing cellular aging and UVB-induced DNA fragmentation. Among the study participants, improvements were found in all of the assessment parameters, with hydration noted as significantly improving right after the first application.

The authors concluded that the yeast Kluyveromyces biopeptides were efficacious in activating SIRT1 in human skin cells, resulting in the enhancement of DNA resistance and aging. In addition, a formulation featuring Kluyveromyces biopeptides exhibited efficacy in ameliorating various signs of cutaneous aging (J. Drugs Dermatol. 2007;6:s14-9).

In 2008, Cao et al. reported on the role of SIRT1 in UV signaling pathways. With cell culture and Western blot analysis, they found that SIRT1 is expressed in cultured human skin keratinocytes. The investigators observed that SIRT1 is time- and dose-dependently down-regulated by exposure to UV radiation and H2O2, with reactive oxygen species (ROS)-mediated JNK (c-Jun N-terminal kinase) activation involved in the down-regulation. Significantly, resveratrol, an activator of SIRT1, protected against UV- and H2O2-induced apoptosis; SIRT inhibitors such as sirtinol and nicotinamide promoted apoptosis.

The investigators also noted that resveratrol suppresses UV- and H2O2-induced p53 acetylation, while the SIRT inhibitors sirtinol and nicotinamide, as well as SIRT1 small interfering RNA (siRNA), foster it. Overall, the researchers suggested that their work adds to the understanding of the molecular mechanisms of photoaging, and that the SIRT1-activating property of resveratrol might be targeted in agents intended for therapeutic approaches to cutaneous aging (J. Cell Mol. Med. 2008 Aug 4 [doi:10.1111/j.1582-4934.2008.00453.x]).

Also in 2008, Pallàs et al. found that increasing SIRT1 protects against amyloid beta-induced ROS synthesis and DNA damage, thus diminishing in vitro apoptosis. In addition, the overexpression of SIRT1, induced by caloric restriction or the use of the antioxidant resveratrol, has been shown to rescue Alzheimer's and Huntington's disease neurons (Recent Pat. CNS Drug Discov. 2008;3:61-9). SIRT1 and SIR2 had already been implicated as the proteins involved in lifespan extension from caloric restriction in various species.

Polyphenols such as quercetin and resveratrol are dietary antioxidants known to confer numerous health benefits and to activate sirtuins, thus playing a role in the caloric restriction longevity extension mechanism; their capacity to influence or extend lifespan has been shown in simple organisms but not consistently, as yet, in humans or other mammals (J. Cosmet. Dermatol. 2008;7:2-7; Genes Nutr. 2006;1:85-93).

However, work in mice (discussed in an episode of the television show "60 Minutes" in early 2009) performed by Sirtris Pharmaceuticals, a research company founded on recent discoveries related to sirtuins, demonstrated that resveratrol fed to mice on a high-fat diet improved insulin resistance, increased mitochondrial content, and prolonged life. In two groups of mice fed a high-fat diet, both groups wound up obese, but the mice administered resveratrol as part of their diet were able to run twice as far and fast, and survived 20% longer. In other studies by Sirtris, mice fed resveratrol as part of a high-fat diet gained less weight than mice administered a high-fat diet without resveratrol. Investigators at Sirtris also have identified small-molecule activators of SIRT1 that are 1,000 times as strong as resveratrol (Nature 2007;450:712-6).

Many other companies, such as Avon, have studied ingredients that upregulate sirtuin expression. By using human skin biopsies and immunohistochemical analysis, Avon has shown that its own proprietary botanical extracts promote the expression of dermal matrix proteins. The company claims that a 12-week clinical study using a product formulated to stimulate sirtuin expression displayed efficacy that warrants use in an antiaging product.

It remains to be seen what such claims - and products - will mean for the skin. For now, I would continue to recommend oral resveratrol and red wine supplements. In particular, I suggest OPC Synergy by Standard Process Inc., which contains grape seed and red wine extracts.

Conclusions
The family of proteins known as sirtuins appears to play an important role in the increased lifespan of various species, particularly, as recent research suggests, in calorie-restricted animals. The polyphenolic antioxidant resveratrol, which is abundant in red wine and is now included in some cosmeceutical agents, upregulates sirtuin expression and may protect cells from DNA damage.

The discovery of the role of sirtuin expression in slowing the pace of aging, in the experimental setting, strikes me as a very significant advance, and may lead to further elucidation of the aging process overall as well as cutaneous aging.

However, it is unknown at this time what role sirtuin and sirtuin activators play in skin care. Early data suggest that the activation of sirtuins may improve the appearance of skin, but the mechanism, if known, is unclear to me. The potential of Avon's botanically derived agent in upregulating sirtuin expression in skin cell cultures appears promising, because the company's study did reveal that patients experienced improvement in wrinkles. I was not the investigator in this study, so it is difficult to comment on the validity of the observations, as I am unsure of the exact study design.

I will be interested to see further work in this area, and it's always good to have a medically sound reason to drink wine.

Recently, investigators attempted to stimulate the expression of sirtuin, specifically SIRT1, in human skin cells in a culture of yeast Kluyveromyces biopetides, and to identify cutaneous benefits from an active skin care product containing such biopeptides. They also tested healthy skin samples ex vivo. Immunostaining, Western blotting, and cytometry were used to assess SIRT1 in culture and in ex vivo samples. Comet assays were used to evaluate cellular aging and integrity. Sir2 protein (Sir2p), present in yeast, is the founding member of the sirtuin family. SIRT1 was the first homolog found in humans and other mammals (Mol. Endocrinol. 2007;21:1745-55; Mol. Cell Biol. 2003;23:3173-85; Biochem. Biophys. Res. Commun. 2000;273:793-8). Now there are seven known mammalian sirtuins: SIRT1-SIRT7. Sirtuins are found in organisms ranging from bacteria to humans. Much sirtuin research has been done in the yeast Saccharomyces cerevisiae, the fruit fly Drosophila melanogaster, and the nematode Caenorhabditis elegans. In these organisms, sirtuins have been identified as molecules that mediate the effects of caloric restriction on aging processes (Genes Nutr. 2006;1:85-93).

Everyone in the skin care world is talking about sirtuins. Studies have shown that resveratrol activates sirtuins, and sales of resveratrol have risen. Many products claim to contain ingredients that activate sirtuins.

To be up to date on current skin care, you need to know what sirtuins are and why they are a frequent topic at the Society of Cosmetic Chemists meetings. The short explanation is that calorie-restricted mice have been shown to live longer and to have increased expression of sirtuins. It is believed that the upregulation of sirtuin expression is associated with increased longevity. When mice were not calorie restricted but were treated with resveratrol to activate sirtuins, they also lived longer.

The current belief that activating sirtuin is desirable has led to a plethora of products with sirtuin-activating ingredients, including several sold by Avon Products Inc.

Where Are Sirtuins Found?

Role of Sirtuins
Silent mating type information regulator 2 (Sir2) proteins, or sirtuins, are a family of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes known to deacetylate lysine residues on several proteins and, in some cases, to exhibit adenosine diphosphate (ADP)-ribosyltransferase activity (Genome Biol. 2004;5:224; Mol. Endocrinol. 2007;21:1745-55). Sirtuins are activated when cellular energy is low and the NAD+ to NADH ratio is high (Genes Nutr. 2006;1:85-93).

This family of enzymes is known to be involved in apoptosis, fatty acid metabolism, gene silencing, and regulation of cellular lifespans. They are also linked to genes that organize and optimize cell functions to resist or survive in stressful environments (J. Drugs Dermatol. 2007;6:s14-9). Sirtuins regulate important biological pathways, such as transcriptional repression, recombination, the cell-division cycle, microtubule organization, and cellular responses to DNA-damaging compounds (Genome Biol. 2004;5:224).

It is believed that the mammalian sirtuins, SIRT1-SIRT7, play an influential role in gene silencing, energy homeostasis, the cell cycle, apoptosis, stress resistance or stress responses, axonal degeneration, and aging (Genome Biol. 2004;5:224; Mol. Endocrinol. 2007;21:1745-55; J. Cell Mol. Med. 2008 Aug 4 [doi:10.1111/j.1582-4934.2008.00453.x ]). As such, Yamamoto et al. have contended that sirtuins may be appropriate therapeutic targets for a range of disorders, including proliferative, neurodegenerative, and metabolic diseases (Mol. Endocrinol. 2007;21:1745-55).

The Nomenclature

Sirtuin Research in Skin

For the active skin care product portion of the study, the researchers enrolled 33 women between 37 and 64 years old (mean age 51.6 years), who were instructed to apply a formulation enriched in 1% of the yeast biopeptides once daily for 4 weeks to the neck and face. Before and after the first application and after 4 weeks of use, investigating dermatologists assessed fine lines and wrinkles, pigment color intensity, complexion homogeneity, and radiance, as well as skin density, hydration, firmness, and texture on a 1-9 scale. To objectively evaluate skin care efficacy, they used a pixel skin method based on analyzing age-related parameters from numerical pictures of faces.

The investigators identified multiple findings from their study. In particular, the Kluyveromyces biopeptides markedly increased SIRT1 expression in normal human dermal fibroblasts in vitro as well as in healthy human epidermal cells ex vivo while diminishing cellular aging and UVB-induced DNA fragmentation. Among the study participants, improvements were found in all of the assessment parameters, with hydration noted as significantly improving right after the first application.

The authors concluded that the yeast Kluyveromyces biopeptides were efficacious in activating SIRT1 in human skin cells, resulting in the enhancement of DNA resistance and aging. In addition, a formulation featuring Kluyveromyces biopeptides exhibited efficacy in ameliorating various signs of cutaneous aging (J. Drugs Dermatol. 2007;6:s14-9).

In 2008, Cao et al. reported on the role of SIRT1 in UV signaling pathways. With cell culture and Western blot analysis, they found that SIRT1 is expressed in cultured human skin keratinocytes. The investigators observed that SIRT1 is time- and dose-dependently down-regulated by exposure to UV radiation and H2O2, with reactive oxygen species (ROS)-mediated JNK (c-Jun N-terminal kinase) activation involved in the down-regulation. Significantly, resveratrol, an activator of SIRT1, protected against UV- and H2O2-induced apoptosis; SIRT inhibitors such as sirtinol and nicotinamide promoted apoptosis.

The investigators also noted that resveratrol suppresses UV- and H2O2-induced p53 acetylation, while the SIRT inhibitors sirtinol and nicotinamide, as well as SIRT1 small interfering RNA (siRNA), foster it. Overall, the researchers suggested that their work adds to the understanding of the molecular mechanisms of photoaging, and that the SIRT1-activating property of resveratrol might be targeted in agents intended for therapeutic approaches to cutaneous aging (J. Cell Mol. Med. 2008 Aug 4 [doi:10.1111/j.1582-4934.2008.00453.x]).

Also in 2008, Pallàs et al. found that increasing SIRT1 protects against amyloid beta-induced ROS synthesis and DNA damage, thus diminishing in vitro apoptosis. In addition, the overexpression of SIRT1, induced by caloric restriction or the use of the antioxidant resveratrol, has been shown to rescue Alzheimer's and Huntington's disease neurons (Recent Pat. CNS Drug Discov. 2008;3:61-9). SIRT1 and SIR2 had already been implicated as the proteins involved in lifespan extension from caloric restriction in various species.

Polyphenols such as quercetin and resveratrol are dietary antioxidants known to confer numerous health benefits and to activate sirtuins, thus playing a role in the caloric restriction longevity extension mechanism; their capacity to influence or extend lifespan has been shown in simple organisms but not consistently, as yet, in humans or other mammals (J. Cosmet. Dermatol. 2008;7:2-7; Genes Nutr. 2006;1:85-93).

However, work in mice (discussed in an episode of the television show "60 Minutes" in early 2009) performed by Sirtris Pharmaceuticals, a research company founded on recent discoveries related to sirtuins, demonstrated that resveratrol fed to mice on a high-fat diet improved insulin resistance, increased mitochondrial content, and prolonged life. In two groups of mice fed a high-fat diet, both groups wound up obese, but the mice administered resveratrol as part of their diet were able to run twice as far and fast, and survived 20% longer. In other studies by Sirtris, mice fed resveratrol as part of a high-fat diet gained less weight than mice administered a high-fat diet without resveratrol. Investigators at Sirtris also have identified small-molecule activators of SIRT1 that are 1,000 times as strong as resveratrol (Nature 2007;450:712-6).

Many other companies, such as Avon, have studied ingredients that upregulate sirtuin expression. By using human skin biopsies and immunohistochemical analysis, Avon has shown that its own proprietary botanical extracts promote the expression of dermal matrix proteins. The company claims that a 12-week clinical study using a product formulated to stimulate sirtuin expression displayed efficacy that warrants use in an antiaging product.

It remains to be seen what such claims - and products - will mean for the skin. For now, I would continue to recommend oral resveratrol and red wine supplements. In particular, I suggest OPC Synergy by Standard Process Inc., which contains grape seed and red wine extracts.

Conclusions
The family of proteins known as sirtuins appears to play an important role in the increased lifespan of various species, particularly, as recent research suggests, in calorie-restricted animals. The polyphenolic antioxidant resveratrol, which is abundant in red wine and is now included in some cosmeceutical agents, upregulates sirtuin expression and may protect cells from DNA damage.

The discovery of the role of sirtuin expression in slowing the pace of aging, in the experimental setting, strikes me as a very significant advance, and may lead to further elucidation of the aging process overall as well as cutaneous aging.

However, it is unknown at this time what role sirtuin and sirtuin activators play in skin care. Early data suggest that the activation of sirtuins may improve the appearance of skin, but the mechanism, if known, is unclear to me. The potential of Avon's botanically derived agent in upregulating sirtuin expression in skin cell cultures appears promising, because the company's study did reveal that patients experienced improvement in wrinkles. I was not the investigator in this study, so it is difficult to comment on the validity of the observations, as I am unsure of the exact study design.

I will be interested to see further work in this area, and it's always good to have a medically sound reason to drink wine.

Recently, investigators attempted to stimulate the expression of sirtuin, specifically SIRT1, in human skin cells in a culture of yeast Kluyveromyces biopetides, and to identify cutaneous benefits from an active skin care product containing such biopeptides. They also tested healthy skin samples ex vivo. Immunostaining, Western blotting, and cytometry were used to assess SIRT1 in culture and in ex vivo samples. Comet assays were used to evaluate cellular aging and integrity. Sir2 protein (Sir2p), present in yeast, is the founding member of the sirtuin family. SIRT1 was the first homolog found in humans and other mammals (Mol. Endocrinol. 2007;21:1745-55; Mol. Cell Biol. 2003;23:3173-85; Biochem. Biophys. Res. Commun. 2000;273:793-8). Now there are seven known mammalian sirtuins: SIRT1-SIRT7. Sirtuins are found in organisms ranging from bacteria to humans. Much sirtuin research has been done in the yeast Saccharomyces cerevisiae, the fruit fly Drosophila melanogaster, and the nematode Caenorhabditis elegans. In these organisms, sirtuins have been identified as molecules that mediate the effects of caloric restriction on aging processes (Genes Nutr. 2006;1:85-93).